High Glycemic Index Diets Linked to CVD and Mortality

People who consume a diet rich in high-glycemic foods, such as white bread, potatoes, and sugary soft drinks, are at an increased risk of cardiovascular events or death from any cause when compared with those who tend to eat foods with a lower glycemic index, such as green vegetables, beans and legumes, and whole grains. The news comes from an analysis of the PURE study.

Glycemic index’s association with adverse cardiovascular outcomes and all-cause mortality was seen in patients with and without preexisting cardiovascular disease, report investigators, and it was most pronounced in individuals who were overweight or obese.

David Jenkins, MD, PhD (University of Toronto, Canada), who led the new analysis, said it reinforces nutritional advice that’s been given for a number of years now—eat quality carbohydrates. “I think this analysis gives people some rationale behind the advice we have been giving for a long time,” he told TCTMD. “Eat your fruit and vegetables, eat whole grains, eat legumes, beans, lentils, and the rest of these sort of foods, and enjoy them. This study strongly provides one reason why these foods are good for you.”

Andrew Freeman, MD (National Jewish Health, Denver, CO), who co-chairs the American College of Cardiology’s Nutrition and Lifestyle working group, said the PURE study’s methodology has been criticized in the past, including by himself and others. Relying on food-frequency questionnaires can provide an inaccurate view of dietary patterns, as they’re based on recall. For example, such questionnaires are notable for underreporting food intake, particularly dietary fat, and this makes it difficult to issue broad statements about links between certain foods, food groups, or nutrients and clinical outcomes.

Despite such limitations, “in this particular case, the simple concept that people who have a higher glycemic diet do worse makes sense based on all the known public data,” Freeman told TCTMD. High-glycemic foods, typically, are highly processed, and these foods are known to significantly increase the risk of adverse cardiovascular outcomes.

“I always tell people there are two types of carbs,” he said. “There’s the good type of carbs—legumes, fruits, and vegetables with lots of fiber in them—and then there’s garbage carbs, or ‘carbage.’ So I think it makes sense that people who might be eating more of the junk food may be doing worse. They might not have access to nutritionally complete foods. We also know that the higher-glycemic foods are typically more shelf stable and cheaper. White rice has a longer shelf life than brown rice, for example, even though [brown rice] is much more nutritious.”

For Freeman, the bottom line is that while there are a number of different associations between diet and clinical outcomes that are not easily captured from the PURE study, showing that eating a nutritionally complete and balanced diet improves cardiovascular health outcomes isn’t one of them.    

Carbs Are Good for You, Carbs Are Bad for You

Several years back, an analysis from PURE suggested that high carbohydrate intake was associated with a significantly increased risk of death. Diets with the most carbohydrates—making up, on average, 77% of daily calories—were associated with a 28% higher risk of death compared with diets that contained lower carbohydrate intake. That study, said Jenkins, led to headlines suggesting that “carbohydrates kill” and increased the popularity of low-carbohydrate diets. Subsequent analyses from PURE, however, also showed that consumption of fruits, vegetables, legumes, and other healthy carbohydrates protected against cardiovascular disease.

Those two studies, Jenkins said, spurred thinking that the disparate carbohydrate findings were part of a “glycemic-index story.” For that reason, Jenkins approached the PURE research group to conduct an analysis focused on the glycemic index and glycemic load of dietary patterns. PURE, he stressed, is an important global study because it includes a diverse patient population across five continents.

This latest analysis, published today in the New England Journal of Medicine, included 137,851 participants ages 35 to 70 years from 20 culturally and socioeconomically diverse countries. Standardized questionnaires were used to collect information about patient demographics, lifestyle, health history, and medication use, and case-report forms were used to collect data regarding major cardiovascular events and all-cause mortality during follow-up. Food intake was collected using different questionnaires specific to the individual country, while nine different questionnaires were specific to various regions of India.

The consumption of diets and specific foods with a high glycemic index, which is the measure of how rapidly food is digested and released as glucose into the bloodstream, was most common in China, followed by Africa and Southeast Asia. Glycemic load, which takes into account the amount of carbohydrate in a serving of food, was highest in South Asia, followed by Africa and China. The mean glycemic index of all study participants was 82.6, and the mean glycemic load was 280.8 g/day.

Overall, participants in the highest quintile of glycemic index (mean 91) had a significant 25% increased risk of the primary endpoint—a composite of cardiovascular death, nonfatal MI, stroke, heart failure, or death from any cause—compared with people in the lowest quintile (mean 76). Major cardiovascular events alone were 14% higher among those in the highest glycemic quintile compared with the lowest. For those without cardiovascular disease at baseline, the relative risk of the primary endpoint was 21% higher in the highest quintile compared with the lowest. Among those with disease at baseline, the relative difference in risk was larger (HR 1.51; 95% CI 1.25-1.82).

There was no significant difference in the risk of the primary endpoint between those with the highest (468 g/day) and lowest (136 g/day) glycemic loads in the overall population. However, among people with preexisting cardiovascular disease, those in the highest quintile of glycemic load had a 34% increased risk of the primary endpoint and a 31% higher risk of major cardiovascular events compared with those in the lowest quintile.

High Glycemic Diet Bad for Overweight Patients

Among patients considered overweight/obese, investigators observed a 38% higher risk of the primary outcome among those with the highest glycemic index versus the lowest. Even among overweight participants with moderately higher glycemic indices, there was an increased risk of the primary outcome compared with the lowest quintile. For those with a BMI < 25 kg/m2, the relationship between glycemic index and clinical outcomes was much weaker.

“The fatter you are, the worse a diet with a high glycemic index is for you,” said Jenkins. “That’s expected.” 

The researchers point out that those with a higher body mass index (BMI) are at increased risk of diabetes, cardiovascular disease, and some cancers. Diets with a high glycemic index could interact with insulin resistance associated with higher BMIs to produce an even larger spike in blood glucose after eating, which would increase the “negative consequences” of eating a diet with a high glycemic index, they write.

To TCTMD, Jenkins said their overall findings were remarkably consistent, and took them by surprise somewhat. A systematic review and meta-analysis published in 2019 failed to find an association between diets characterized by higher glycemic index/load and a range of clinical outcomes, although the number of patients included with glycemic-related data was small, said Jenkins. “The glycemic index just hadn’t been studied that much.” 

What their results boil down to, said Jenkins, is “the quality of the carbohydrate that you put into the diet” matters. While PURE is an observational cohort study and subject to limitations, the researchers were able to control for a wide range of variables because these were measured as part of the study, he added.